Karen Kilcoyne

Karen Kilcoyne
The University of Edinburgh | UoE · MRC Centre for Reproductive Health

About

31
Publications
4,071
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528
Citations
Citations since 2016
24 Research Items
508 Citations
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2016201720182019202020212022020406080100
2016201720182019202020212022020406080100
2016201720182019202020212022020406080100

Publications

Publications (31)
Article
Testicular Leydig cells (LCs) are the principal source of circulating testosterone in males. LC steroidogenesis maintains sexual function, fertility and general health, and is influenced by various paracrine factors. The leukemia inhibitory factor receptor (LIFR) is expressed in the testis and activated by different ligands, including leukemia inhi...
Article
Full-text available
Background Despite the increasing popularity of deliverable transgenics, a robust and fully validated method for targeting Leydig cells, capable of delivering long‐term transgene expression, is yet to be defined. Objectives We compared three viral vector systems in terms of their cell targeting specificity, longevity of gene expression and impact...
Article
Context: The endocrine function of human fetal adrenals (HFA) is activated already during first trimester, but changes in adrenal steroidogenesis during fetal life are not well characterized. Objective: This study aimed to investigate HFA steroidogenesis by analyzing adrenal glands from 1st and 2nd trimester. Design and Setting: Male and female HFA...
Article
Full-text available
Background: Overall, the incidence of male reproductive disorders has increased in recent decades. Testicular development during fetal life is crucial for subsequent male reproductive function. Non-genomic factors such as environmental chemicals, pharmaceuticals and lifestyle have been proposed to impact on human fetal testicular development resul...
Article
Transplantation of testicular tissues and cells has been proposed as a future clinical option for patients who have had testicular tissue cryopreserved prior to receiving gonadotoxic therapies. Whilst this approach remains experimental, success using animal models and successful transplantation of ovarian tissue resulting in live births in female p...
Article
Full-text available
Context The endocrine function of human fetal adrenals (HFA) is activated already during first trimester, but changes in adrenal steroidogenesis during fetal life are not well characterized. Objective This study aimed to investigate HFA steroidogenesis by analyzing adrenal glands from 1st and 2nd trimester. Design and Setting Male and female HFA...
Article
Full-text available
Disruption of human fetal testis development is widely accepted to underlie testicular germ cell cancer (TGCC) origin and additional disorders within testicular dysgenesis syndrome (TDS). However, the mechanisms for the development of testicular dysgenesis in humans are unclear. We used ex vivo culture and xenograft approaches to investigate the im...
Article
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Study question: Does loss of DMRT1 in human fetal testis alter testicular development and result in testicular dysgenesis? Summary answer: DMRT1 repression in human fetal testis alters the expression of key testicular and ovarian determining genes, and leads to focal testicular dysgenesis. What is known already: Testicular dysgenesis syndrome...
Article
Full-text available
Background: Analgesic exposure during pregnancy may affect aspects of fetal gonadal development that are targeted by endocrine disruptors. Objectives: We investigated whether therapeutically relevant doses of acetaminophen and ibuprofen affect germ cell (GC) development in human fetal testes/ovaries using in vitro and xenograft approaches. Meth...
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Background: Using an organotypic culture system termed human Fetal Testis Assay (hFeTA) we previously showed that 0.01 μM BPA decreases basal, but not LH-stimulated, testosterone secreted by the first trimester human fetal testis. The present study was conducted to determine the potential for a long-term antiandrogenic effect of BPA using a xenogr...
Data
Effect of BPA exposure on germ cell apoptosis in mouse fetal testes cultured using the FeTA system. Testes were removed from NMRI mice at 12.5 day-post conception and cultured as previously described using the FeTA system [29,31,48,49]. After 24 hours in control medium, explants were cultured under basal conditions for the subsequent 24 hours in th...
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Full-text available
The insulin family of growth factors (insulin, IGF1, and IGF2) are critical in sex determination, adrenal differentiation, and testicular function. Notably, the IGF system has been reported to mediate the proliferation of steroidogenic cells. However, the precise role and contribution of the membrane receptors mediating those effects, namely, insul...
Article
Full-text available
Human male reproductive disorders (cryptorchidism, hypospadias, testicular cancer and low sperm counts) are common and some may be increasing in incidence worldwide. These associated disorders can arise from subnormal testosterone production during fetal life. This has resulted in a focus on in-utero environmental influences that may result in repr...
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Full-text available
The testicular dysgenesis syndrome (TDS) hypothesis, which proposes that common reproductive disorders of newborn and adult human males may have a common fetal origin, is largely untested. We tested this hypothesis using a rat model involving gestational exposure to dibutyl phthalate (DBP), which suppresses testosterone production by the fetal test...
Article
Full-text available
Among pregnant women ibuprofen is one of the most frequently used pharmaceutical compounds with up to 28% reporting use. Regardless of this, it remains unknown whether ibuprofen could act as an endocrine disruptor as reported for fellow analgesics paracetamol and aspirin. To investigate this, we exposed human fetal testes (7–17 gestational weeks (G...
Article
Introduction: Adult male testosterone levels are influenced by fetal events, but how is unknown, as adult Leydig cells (ALC) do not differentiate until puberty. We hypothesised that adult Leydig stem cells are present in the fetal testis, and are susceptible to programming by fetal androgen exposure. We have shown that ALC derive from interstitial...
Thesis
There is increasing evidence to suggest that fetal events can predetermine reproductive health and general wellbeing in adulthood, a process termed 'fetal programming'. This refers to the association between altered fetal growth/development and health disorders in adulthood e.g. the metabolic syndrome, which is linked to low male testosterone level...
Article
Full-text available
Significance Men are defined by androgens (testosterone), which drive fetal masculinization (male development) and puberty and maintain masculinity in adulthood, including sex drive, erectile function, and fertility. Moreover, Western cardiometabolic diseases are all associated with lowered testosterone levels in men. Therefore, influences on testo...
Article
Differentiation of the testis and its subsequent hormonal function are pivotal events in development of the male, but there is increasing evidence that these events are susceptible to disruption by environmental/lifestyle factors which can then result in (common) reproductive disorders – these are frequently referred to as testicular dysgenesis syn...
Article
During fetal testis development, signaling cascades between various cell types regulate key events such as proliferation, differentiation, cell survival and vascularization, however the signaling pathways regulating these processes are poorly characterized. Prokineticins (PROK1 and PROK2) are recently described ligands that signal interchangeably v...

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